Yeast carries up to five different dsRNAs, called L-A, L-(BC), T, W, and M. Killer strains of yeast secrete a protein toxin to which they are themselves immune. Toxin and immunity are determined by the M dsRNAs: M1 (l.5 kb) for the K1 system and M2 (1.0 kb) for the K2 system. The replication of M1 or M2 depends on L-A (4.5 kb), which encodes the major protein of the virus-like particles in which L-A and M dsRNAs are found. Thirty chromosomal genes (MAK) are necessary for M1 or M2 replication. Two genes (MKT) are specifically needed for M2 and only if L-A-HN is present. We have shown that M dsRNA represses L-A replication but does not affect L-(BC), while the six chromosomal SKI+ gene products repress L-A, L-(BC), and M dsRNA replication, as shown by 3- to l0-fold lowering of their copy numbers. The effect of M on L-A is epistatic to that of SKI products. We have isolated a ski-strain that can maintain M1 in spite of its lacking L-A completely. MAK1 has been shown by others to be the gene for yeast topoisomerase I. Our work showed this gene's involvement in M dsRNA replication (but not L-A, L-B, T, or W). We recently found that all three mutant alleles of MAK1 confer cold sensitivity for cell growth (8 C), although growth is normal from 20 C to 37 C. The gene for yeast topoisomerase II was located by others near MET4 on chromosome XIV. We recently mapped the MKT1 gene on chromosome XIV, also near MET4, and are investigating the possible identity of these two genes. They are at least very close to each other, as no recombination was found in a total of 4l meiotic tetrads. One allele of MKT1, when combined with a particular cytoplasmic element, results in cold sensitivity for cell growth (8 C). Preliminary evidence suggests that the cytoplasmic element is L-(BC). We previously showed that ski- mutants carrying M dsRNA are cold-sensitive for growth because their M copy number is elevated. Using the cold sensitivity of ski- strains carrying M dsRNA, we have cloned segments of yeast DNA that suppress this effect. These should include the SKI+ genes themselves and genes, overproduction of whose products, suppress this phenotype. We have discovered a chromosomal gene affecting the copy number of both T and W dsRNAs.